Evidence map›Paper›PMID 41648231›Full record

ArticlebioRxiv : the preprint server for biology2026

Dysregulated TGFβ-ERK Signaling Drives Aberrant Extracellular Matrix Production in Noonan Syndrome-Associated Pulmonary Valve Stenosis.

Clifford Z Liu, Shrey Patel, Simone Sidoli, Aditi Prasad, Daniel Charytonowicz, Amine Mazine, Alexander A Mikryukov, Jamshid Abdul-Ghafar, Elizabeth S Kahn, Dejauwne Young and 10 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Clifford Z LiuMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0003-1783-299X
Shrey PatelMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Simone SidoliLaboratory for Macromolecular and Proteomics Facility, Albert Einstein College of Medicine, Bronx, NY, USA.ORCID 0000-0001-9073-6641
Aditi PrasadMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Daniel CharytonowiczDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Amine MazineMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.ORCID 0000-0001-9086-9823
Alexander A MikryukovMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Jamshid Abdul-GhafarDepartment of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Elizabeth S KahnThe Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dejauwne YoungLaboratory for Macromolecular and Proteomics Facility, Albert Einstein College of Medicine, Bronx, NY, USA.
George A PorterDepartment of Pediatrics, University of Rochester Medical Center, Rochester, NY, USA.ORCID 0000-0003-0726-9988
Philip J KatzmanDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Stephen P SandersDepartment of Pathology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3521-4044
Chrystalle Katte CarreonDepartment of Pathology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-2152-7998
Dirk HubmacherMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Joy LincolnDepartment of Pediatrics, Section of Pediatric Cardiology, Medical College of Wisconsin, Milwaukee, WI, USA.ORCID 0000-0003-1517-6888
Gordon M KellerMcEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
Wendy K ChungDepartment of Pediatrics, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-3438-5685
Robert SebraDepartment of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Bruce D GelbMindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID 0000-0001-8527-5027

Funding

Conduits: Mount Sinai Health System Translational Science HubUL1TR004419 · NCATS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Rosalind J Wright · 2022 to 2026
$46.4M
Mount Sinai Medical Scientist Training ProgramT32GM146636 · NIGMS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Talia H Swartz · 2022 to 2026
$6.8M
Pediatric Heart Disease: Getting from Mutations to TherapeuticsR35HL135742 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI GELB, BRUCE D · 2017 to 2023
$6.1M
Interdisciplinary Training in Systems and Developmental Biology and Birth DefectsT32HD075735 · NICHD · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI JABS, ETHYLIN WANG · 2013 to 2022
$1.8M
Orbitrap Exploris 480 Basic SystemS10OD030286 · OD · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI SIDOLI, SIMONE · 2021 to 2021
$600k
NCATS NIH HHS UL1 TR004419NHLBI NIH HHS R35 HL135742NICHD NIH HHS T32 HD075735NIGMS NIH HHS T32 GM146636NIH HHS S10 OD030286
6 · The paper itself

Abstract

Pulmonary valve stenosis (PVS) is the most common congenital heart defect in Noonan syndrome (NS) and related RASopathies, yet the molecular mechanisms linking pathogenic variants to the valve pathology remain poorly defined. Here, we utilized a human iPSC-based valve differentiation platform to generate the cardiac valve cell lineages-including fibrosa and spongiosa valve interstitial cell (VIC) subtypes. CRISPR-edited iPSCs harboring NS gain-of-function RAS/MAPK and Noonan syndrome with multiple lentigines (NSML) dominant-negative RAS/MAPK variants exhibited early defects in mesodermal and endocardial specification in all genotypes. Additionally, NS-iPSC endocardial cells exhibited defects in endothelial-to-mesenchymal transition (EndMT) specifically towards fibrosa VICs, which was most pronounced in

Identifiers

PMID41648231
PMCPMC12871759

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.